The association between uncarboxylated matrix Gla protein and lipoprotein-associated phospholipase A2

Maturitas. 2015 Jan;80(1):82-8. doi: 10.1016/j.maturitas.2014.10.003. Epub 2014 Oct 16.

Abstract

Background: Lipoprotein-associated phospholipase A2 (Lp-PLA2) is independently associated with cardiovascular risk, probably via inflammatory activity in sclerotic plaque. We speculated whether Lp-PLA2 has a role in the aetiology of vascular calcifications, estimated from circulating uncarboxylated matrix Gla protein (MGP) species and whether we could find a potential interaction of Lp-PLA2 and MGP in terms of mortality.

Materials and methods: We examined 798 patients (mean age 65.1 years) with stable vascular disease and followed them in a prospective study. Both, desphospho-uncarboxylated and total MGP (dp-ucMGP or t-ucMGP) were quantified by pre-commercial ELISA assays, developed by VitaK (Maastricht, The Netherland)

Results: Lp-PLA2 activity was independently positively associated with desphospho-uncarboxylated MGP (dp-ucMGP) [β coeff = 0.098, p=0.006]. 1SD of Lp-PLA2 activity was associated with 37% increased risk (p=0.001) of elevated dp-ucMGP (≥977 pmol/L, top quartile). In the Cox proportional hazard model adjusted for conventional risk factors, the patients in the highest quartile of dp-ucMGP or lowest quintile of total-uncarboxylated ucMGP (<2660 nmol/L) had higher risk of all-cause mortality [HRR 2.79 (95% CI 1.97-3.94) and HRR 1.69 (95% CI 1.18-2.42), respectively]. We observed no effect of high Lp-PLA2 activity (≥195 nmol/min/mL) on total mortality.

Conclusions: We assume that Lp-PLA2 is involved in vascular calcification and that dp-ucMGP is a more appropriate biomarker of residual risk than Lp-PLA2 itself.

Keywords: Coronary heart disease; Euroaspire; Lipoprotein-associated phospholipaseA(2); Matrix Gla protein; Mortality risk; Stroke.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Alkyl-2-acetylglycerophosphocholine Esterase / blood*
  • Aged
  • Biomarkers / blood*
  • Calcium-Binding Proteins / blood*
  • Cardiovascular Diseases / blood*
  • Cardiovascular Diseases / mortality
  • Extracellular Matrix Proteins / blood*
  • Female
  • Humans
  • Male
  • Matrix Gla Protein
  • Middle Aged
  • Netherlands
  • Proportional Hazards Models
  • Prospective Studies
  • Risk Factors
  • Survival Analysis

Substances

  • Biomarkers
  • Calcium-Binding Proteins
  • Extracellular Matrix Proteins
  • 1-Alkyl-2-acetylglycerophosphocholine Esterase